Chitosan has been emerging as a promising biomaterial for a multitude of tissue regeneration and drug delivery applications (Prabaharan, 2008, Journal of Biomaterials Applications, 23: 5; Seo et al., 2008, Biotechnol Adv, 26: 1). The extensive research on chitosan has led to the development of many fabrication methods for the preparation of microparticles, nanoparticles, films, sponges, nanofibers, microfibers, and hydrogels (Panoe et al., 2008, Curr Drug Discov Technol, 5: 333; Bhattarai et al., 2010, Adv Drug Deliver Rev, 62: 83). This ability to fabricate chitosan using different methods makes it one of the most versatile naturally-derived biomaterials currently used. Chitosan sponges, specifically, are promising scaffolds for bone and cartilage tissue regeneration (Silva et al., 2008, Biomacromolecules, 9: 2765; Park et al., 2000, Biomaterials, 21: 153), and for a wide range of drug delivery applications (Arpornmaeklong et al., 2008, Int J Oral Max Surg, 37: 357; Pereira et al., 2005. Curr Drug Discov Technol, 2: 231; Ding et al., 2008, Process Biochem, 43: 287). Implantation of these sponges in situ is usually done via an invasive surgical procedure that requires recovery time and potential for infection during the wound healing process (Chesnutt et al., 2009, Tissue engineering. Part A, 15: 2571). Therefore, a minimally invasive procedure to form chitosan scaffolds in situ is desirable.
Injectable chitosan hydrogels have been widely explored in the literature, and stimuli, such as temperature, pH and UV-irradiation, have been used to trigger gelation in situ (Vaghani et al., 2012, Carbohyd Res, 347: 76; Tsuda et al., 2009, Artif Organs, 33:74). However, a fast rate of gelation, a key requirement, still remains less than ideal. A fast rate of gelation is desirable to keep the hydrogel localized at the site of injection. Thermosensitive Chitosan/β-Glycerophosphate hydrogels, extensively studied in the literature, were shown to gel in 4-9 minutes at 37° C. (Crompton et al., 2005, Biophys Chem, 117: 47). Another example is PEG-grafted chitosan that was shown to undergo a sol-gel transition in 10±4 minutes (Bhattarai et al., 2005, Journal of Controlled Release, 103: 609).
There is thus still a need to be provided with chitosan scaffolds or hydrogels with improved gelation properties.